Pathways of phospholipid oxidation by HOCl in human LDL detected by LC-MS

A wealth of evidence now indicates that low-density lipoprotein (LDL) must be modified to promote atherosclerosis, and that this may involve oxidants released by phagocytes. Many studies of oxidative damage in atherosclerosis previously have concentrated on damage by nonhalogenated oxidants, but HOC l is a highly toxic oxidant produced by myeloperoxidase in phagocytes, whic h is also likely to be important in the disease pathogenesis. Currently som e controversy exists over the products resulting from reaction of HOCl with LDL lipids, in particular regarding whether predominantly chlorohydrins or lipid peroxides are formed. In this study LC-MS of phosphatidylcholines in human LDL treated either with HOCl or the myeloperoxidase system was used as a specific method to detect chlorohydrin and peroxide formation simultan eously, and with comparable sensitivity. Chlorohydrin products from lipids containing oleic, linoleic and arachidonic acids were detected, but no hydr operoxides of linoleoyl or arachidonoyl lipids could be observed. This stud y provides the first direct evidence that lipid chlorohydrins rather than p eroxides are the major products of HOCl- or myeloperoxidase-treated LDL pho spholipids. This in turn provides important information required for the st udy of oxidative damage in vivo which will allow the type and source of oxi dants involved in the pathology of atherosclerosis to be investigated. (C) 2000 Elsevier Science Inc.